I’ve observed before that the common belief that viruses evolve toward avirulence is not particularly true. It’s more accurate to say that viruses evolve toward improved transmission. Some viruses are better transmitted if they let their host survive longer, but other viruses have to be virulent in order to spread. The former may evolve toward reduced (though not necessarily loss of) virulence, but the latter would “want” to maintain stable virulence.

What about increasing viral virulence? What could drive that?

There’s at least one fairly well-documented example of that. The increase in virulence is probably because of a change in the virus’s environment thatÂ forces the virus to become more virulent in order to continue to transmit efficiently. Ironically, the environmental change is vaccination.

As far as I know — I want to put this up front, to forestall the vaccine loons — there’s no instance where this has happened with a vaccine used for humans. 1 I’m talking about a chicken vaccine, for Marek’s Disease.

Marek’s Disease Virus (MDV) is an extraordinarily interesting virus. It’s a herpesvirus of chickens; it causes, among other symptoms, tumors. MDV was a relatively minor problem when chicken farming was a backyard industry. When very large, intensive commercial chicken farms arose, the virus was able to sweep through flocks and cause truly enormous losses. The first Marek’s Disease vaccine, introduced in the 1960s, reduced losses by some 99%. (Incidentally, this was the first vaccine ever to prevent cancer.)

But the 99% protection rate didn’t last long. Losses began to creep up once again, as more virulent viruses arose. New vaccines have been introduced a couple times; each time losses dropped, but then once again new and increasingly-virulent viruses arose. Marek’s Disease viruses isolated today are far more virulent than the relatively benign viruses of the 1960s and early 1970s; the original vaccine is essentially useless against them.

The figure at right2 (click for a larger version) shows the virulence of virus strains isolated over a ten-year period — although there’s a lot of variability, there’s a pretty clear upward trend. (This chart — and all the others I could find — only shows changes relatively late in the story, skipping the interesting periods in the 1970s and early 1980s when the first changes in virulence were noted. I think this is a technical issue of having the appropriate strains available for comparison. However, see: Increased virulence of Marek’s disease virus field isolates. Witter RL. Avian Dis. 1997 Jan-Mar;41(1):149-63. doi:10.1016/j.tvjl.2004.05.009 for a more detailed analysis of MDV strain virulence over the years.)

This evolution is actually very reminiscent of the myxoma/rabbit co-evolution story I’ve talked about, here and here. Australian rabbits have evolved to become much more resistant to myxoma virus than their European cousins. In this case, MDV is more analogous to the rabbits than to myxoma — evolving mechanisms to persist and replicate in the face of a lethal challenge (for the rabbits, myxoma virus; for Marek’s Disease virus, the vaccine-derived immunity).

Before rabbits could evolve resistance, there had to be some survivors of myxoma infection. In that case, myxoma virus itself evolved to become somewhat less virulent (70-90% lethal, instead of 98%). In the Marek’s Disease story, a key factor is that the vaccines all suck3 in their ability to actually prevent infection; they prevent the disease, but viruses can still infect vaccinated birds, although the virus replicates slower (which reduces transmission).

This is a recipe for virulence. Viruses in general evolve toward improved transmission. The MDV vaccine reduces, but doesn’t eliminate, transmission. Increasing replication in the face of the vaccine increases transmission. Increasing viral replication also increases viral virulence.4

This probably isn’t the whole story (there’s some evidence that the virus was already evolving toward increased virulence even before the vaccine was introduced — perhaps related to changes in its environment brought about by factory farming), and the mechanisms underlying the changes in virulence are not known, but the solution would seem to be clear: Develop a Marek’s Disease vaccine that will induce sterilizing immunity, as do most vaccines used against human viruses. That way, there’s no survivor virus that can act as a seed for evolution of virulence.

Unfortunately, of course, herpesviruses like MDV are notoriously difficult to vaccinate against. There’s still no commercial vaccine against herpes simplex virus, in spite of decades of research. Feline herpesvirus vaccine, which is universally used among pet cats, is like Marek’s in that it prevents symptoms but doesn’t prevent infection. (There is an effective vaccine against varicella-zoster virus [chicken pox] which does seem to effectively prevent infection — an exception to the rules.) So the chicken world is forced to stick with the non-sterilizing vaccines, even though “MD vaccines also appear to have a malign inï¬‚uence on the continued evolution of the pathogen itself.” 2

I don’t think Varivax (the anti-chicken pox vaccine) prevents infection. Its FDA approval is based on a reduction of serious infections. Not the overall number of infections. Vaccinated kids still get chicken pox, but they get far fewer lesions and are far less systemically ill. I had never thought about the issue you raise here before (possibly because I’m not a virologist or an immunologist)… but this actually raises a red flag around universal vaccination against varicella.

Are you sure about that? I thought it does prevent infection with wild-type virus. In general herpesviruses don’t superinfect well (though it does happen) and since the vaccine virus establishes its own persistent infection I’d expect that superinfection with wild-type virus would be rare. If I’m interpreting a number of papers correctly, this is correct — superinfection with wild-type virus does occur but it’s unusual, a few percent, and associated with reduced disease — but almost everything I find does look more at disease than evidence of infection.

Testing for superinfection would probably be very difficult, because you can’t use the usual seroconversion measures; you’d have to actually sequence out virus and confirm that it’s wild-type and not vaccine strain. I believe that it’s this technical difficulty that’s led to the FDA definition of preventing disease rather than infection.

[…] influenza and norovirus, both tend to have fairly short-term immunity to start with. Something like Marek’s Disease of chickens would be an interesting case study, but the logistics of the poultry agribusiness is […]

The occurence of virus cannot be avoided bu the spread of virus can be prevented. There are a lot of causes and effects that may occur in different age group. The best treatment is having a clean and secured environment together with proper hygiene and healthy foods. Keep in mind that a lot of people may not easily understand the how virus occur.